title: Induction of TLR4-dependent CD8+ T cell immunity by murine β-defensin2 fusion protein vaccines.
abstract: Our laboratory previously described the strategy of fusing chemokine receptor ligands to antigens in order to generate immunogenic DNA vaccines. In the present study, we produced mouse β-2 defensin (mBD2) fusion proteins using both ovalbumin (OVA) and gp100 as model antigens. Superior cross-presentation by dendritic cells (DC) was observed for mBD2 fused antigens over unfused antigens in vitro. In vivo, we observed significant increases in the expansion of adoptively transferred antigen-specific MHC class I, but not class II-restricted T cells after immunization with mBD2 fused antigen over antigen alone. This enhanced expansion of class I restricted T cells was Toll-like receptor 4 (TLR4) dependent, but CC chemokine receptor 6 (CCR6) independent. Superior tumor resistance was observed for mBD2-fusion protein vaccines, compared to unfused antigen, in both B16-OVA and B16 tumor models. These data suggest that production of mBD2 fusion proteins is feasible and that the vaccines facilitate in vivo expansion of adoptively transferred T cells through a TLR4-dependent mechanism.
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Park
authors.forename: H
authors.initials: H
authors.lastname: Qin
authors.forename: S C
authors.initials: SC
authors.lastname: Cha
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.forename: Y
authors.initials: Y
authors.lastname: Chung
authors.forename: K S
authors.initials: KS
authors.lastname: Schluns
authors.forename: S S
authors.initials: SS
authors.lastname: Neelapu
authors.forename: W W
authors.initials: WW
authors.lastname: Overwijk
authors.forename: P
authors.initials: P
authors.lastname: Hwu
authors.forename: L W
authors.initials: LW
authors.lastname: Kwak
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045142:Cross-Priming; D007371:Interferon-gamma / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D054399:Receptors, CCR6 / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D023083:beta-Defensins / Q000276:immunology*; D058951:gp100 Melanoma Antigen / Q000276:immunology
chemical_list: C498126:CCR6 protein, mouse; D019496:Cancer Vaccines; C117047:Defb2 protein, mouse; D054399:Receptors, CCR6; D011993:Recombinant Fusion Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D023083:beta-Defensins; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma; D010047:Ovalbumin